Frank Behrensmeier

Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy

PURPOSE To determine the acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and present short-term biochemical no evidence of disease (bNED) rates after high-dose-rate brachytherapy (HDR-B) monotherapy. METHODS AND MATERIALS Between October 2003 and June 2006, 36 patients with low (28) and intermediate (8) risk prostate cancer (PCA) were treated by HDR-B monotherapy. All patients received one implant and four fractions of 9.5Gy within 48h for a total prescribed dose (PD) of 38Gy. Five patients received hormonal therapy (HT). Median age was 63.5 years and median followup was 3 years (range, 0.4-4 years). Toxicity was scored according to the CTCAE version 3.0. Biochemical failure was defined according to the Phoenix criteria. RESULTS Acute and late Grade 3 GU toxicity was observed in 1 (3%) and 4 (11%) patients, respectively. Grade 3 GI toxicity was absent. The three- year bNED survival rate was 100%. The sexual preservation rate in patients without HT was 75%. Late Grade 3 GU toxicity was associated with the planning target volume (PTV) V(100) (% PTV receiving > or =100% of the PD; p=0.036), D(90) (dose delivered to 90% of the PTV; p=0.02), and the urethral V(120) (urethral volume receiving > or =120% of the PD; p=0.043). The urethral V(120) was associated with increased PTV V(100) (p<0.001) and D(90) (p=0.003). CONCLUSIONS After HDR-B monotherapy, late Grade 3 GU toxicity is associated with the urethral V(120) and the V(100) and D(90) of the PTV. Decrease of the irradiated urethral volume may reduce the GU toxicity and potentially improve the therapeutic ratio of this treatment.

Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

INTRODUCTION To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years. RESULTS Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V(120) (urethral volume receiving > or =120% of the prescribed HDR-B dose) was associated with acute (P=.047) and late > or = grade 2 GU toxicities (P=.049). CONCLUSIONS Late grades 3 and 4GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V(120) on GU toxicity should be validated in further studies.

High Dose-Rate Versus Low Dose-Rate Brachytherapy for Lip Cancer

PURPOSE To analyze the outcome after low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy for lip cancer. METHODS AND MATERIALS One hundred and three patients with newly diagnosed squamous cell carcinoma of the lip were treated between March 1985 and June 2009 either by HDR (n = 33) or LDR brachytherapy (n = 70). Sixty-eight patients received brachytherapy alone, and 35 received tumor excision followed by brachytherapy because of positive resection margins. Acute and late toxicity was assessed according to the Common Terminology Criteria for Adverse Events 3.0. RESULTS Median follow-up was 3.1 years (range, 0.3-23 years). Clinical and pathological variables did not differ significantly between groups. At 5 years, local recurrence-free survival, regional recurrence-free survival, and overall survival rates were 93%, 90%, and 77%. There was no significant difference for these endpoints when HDR was compared with LDR brachytherapy. Forty-two of 103 patients (41%) experienced acute Grade 2 and 57 of 103 patients (55%) experienced acute Grade 3 toxicity. Late Grade 1 toxicity was experienced by 34 of 103 patients (33%), and 5 of 103 patients (5%) experienced late Grade 2 toxicity; no Grade 3 late toxicity was observed. Acute and late toxicity rates were not significantly different between HDR and LDR brachytherapy. CONCLUSIONS As treatment for lip cancer, HDR and LDR brachytherapy have comparable locoregional control and acute and late toxicity rates. HDR brachytherapy for lip cancer seems to be an effective treatment with acceptable toxicity.

Acute and late toxicity in prostate cancer patients treated by dose escalated intensity modulated radiation therapy and organ tracking

BackgroundTo report acute and late toxicity in prostate cancer patients treated by dose escalated intensity-modulated radiation therapy (IMRT) and organ tracking.MethodsFrom 06/2004 to 12/2005 39 men were treated by 80 Gy IMRT along with organ tracking. Median age was 69 years, risk of recurrence was low 18%, intermediate 21% and high in 61% patients. Hormone therapy (HT) was received by 74% of patients. Toxicity was scored according to the CTC scale version 3.0. Median follow-up (FU) was 29 months.ResultsAcute and maximal late grade 2 gastrointestinal (GI) toxicity was 3% and 8%, late grade 2 GI toxicity dropped to 0% at the end of FU. No acute or late grade 3 GI toxicity was observed. Grade 2 and 3 pre-treatment genitourinary (GU) morbidity (PGUM) was 20% and 5%. Acute and maximal late grade 2 GU toxicity was 56% and 28% and late grade 2 GU toxicity decreased to 15% of patients at the end of FU. Acute and maximal late grade 3 GU toxicity was 8% and 3%, respectively. Decreased late ≥ grade 2 GU toxicity free survival was associated with higher age (P = .025), absence of HT (P = .016) and higher PGUM (P < .001).DiscussionGI toxicity rates after IMRT and organ tracking are excellent, GU toxicity rates are strongly related to PGUM.

Applicability and dosimetric impact of ultrasound-based preplanning in high-dose-rate brachytherapy of prostate cancer

Background and Purpose:Analyses of permanent brachytherapy seed implants of the prostate have demonstrated that the use of a preplan may lead to a considerable decrease of dosimetric implant quality. The authors aimed to determine whether the same drawbacks of preplanning also apply to high-dose-rate (HDR) brachytherapy.Patients and Methods:15 patients who underwent two separate HDR brachytherapy implants in addition to external-beam radiation therapy for advanced prostate cancer were analyzed. A pretherapeutic transrectal ultrasound was performed in all patients to generate a preplan for the first brachytherapy implant. For the second brachytherapy, a subset of patients were treated by preplans based on the ultrasound from the first brachytherapy implant. Preplans were compared with the respective postplans assessing the following parameters: coverage index, minimum target dose, homogeneity index, and dose exposure of organs at risk. The prostate geometries (volume, width, height, length) were compared as well.Results:At the first brachytherapy, the matching between the preplan and actual implant geometry was sufficient in 47% of the patients, and the preplan could be applied. The dosimetric implant quality decreased considerably: the mean coverage differed by –0.11, the mean minimum target dose by –0.15, the mean homogeneity index by –0.09. The exposure of organs at risk was not substantially altered. At the second brachytherapy, all patients could be treated by the preplan; the differences between the implant quality parameters were less pronounced. The changes of prostate geometry between preplans and postplans were considerable, the differences in volume ranging from –8.0 to 13.8 cm3 and in dimensions (width, height, length) from –1.1 to 1.0 cm.Conclusion:Preplanning in HDR brachytherapy of the prostate is associated with a substantial decrease of dosimetric implant quality, when the preplan is based on a pretherapeutic ultrasound. The implant quality is less impaired in subsequent implants of fractionated brachytherapy.Hintergrund und Ziel:Die Anwendung eines Preplan bei der Prostata-Brachytherapie mit radioaktiven Seeds geht häufig mit einer relevanten Abnahme der dosimetrischen Qualität des Implantats einher. Es wird untersucht, ob bei der High-Dose-Rate- (HDR-)Brachytherapie dieselben Nachteile des Preplannings auftreten.Patienten und Methodik:Die Studie stützt sich auf 15 Patienten mit einem fortgeschrittenen Prostatakarzinom, die mit externer Strahlentherapie und zwei HDR-Brachytherapie-Sitzungen behandelt wurden. Alle Patienten wurden mit prätherapeutischem transrektalem Ultraschall als Basis zur Erstellung eines Preplan für die erste Brachytherapie untersucht. Die zweite Brachytherapie wurde in einer Subgruppe (n = 6) mittels Preplan appliziert, der auf dem Ultraschall der ersten Brachytherapie basierte (Abbildung 1). Die Preplans wurden mit den entsprechenden Postplans auf folgende Parameter hin verglichen: Coverage-Index, minimale Target-Dosis, Homogenitätsindex und Dosisbelastung der Risikoorgane. Ebenso wurden die geometrischen Maße der Prostata verglichen (Volumen, Breite, Höhe, Länge).Ergebnisse:Bei 47% der Patienten wurde die Übereinstimmung der Implantatgeometrie von Preplan und erster Brachytherapiesitzung als ausreichend erachtet, und der Preplan konnte nachfolgend angewendet werden. Die Implantatqualität nahm deutlich ab (Tabelle 1): Der mittlere Coverage-Index sank um –0,11, die mittlere Target-Dosis um –0,15, der mittlere Homogenitätsindex um –0,09. Die Strahlenbelastung der Risikoorgane erhöhte sich nicht wesentlich (Tabelle 2). Die Unterschiede der geometrischen Parameter waren beträchtlich (–8,0 bis 13,8 cm3 betreffend Volumen; –1,1 bis 1,0 cm betreffend Breite, Höhe und Länge; Abbildung 2 und Tabelle 3).Schlussfolgerung:Die Verwendung eines Preplan in der HDR-Brachytherapie der Prostata resultiert in einer wesentlichen Abnahme der Implantatqualität, wenn der Preplan auf einem prätherapeutischen Ultraschall basiert. Diese Abnahme ist bei fraktionierter Behandlung in nachfolgenden Brachytherapiesitzungen weniger ausgeprägt.

Use of Gold Markers for Setup in Image-Guided Fractionated High-Dose-Rate Brachytherapy as a Monotherapy for Prostate Cancer

Background and Purpose:In order to use a single implant with one treatment plan in fractionated high-dose-rate brachytherapy (HDR-B), applicator position shifts must be corrected prior to each fraction. The authors investigated the use of gold markers for X-ray-based setup and position control between the single fractions.Patients and Methods:Caudad-cephalad movement of the applicators prior to each HDR-B fraction was determined on radiographs using two to three gold markers, which had been inserted into the prostate as intraprostatic reference, and one to two radiopaque-labeled reference applicators. 35 prostate cancer patients, treated by HDR-B as a monotherapy between 10/2003 and 06/2006 with four fractions of 9.5 Gy each, were analyzed. Toxicity was scored according to the CTCAE Score, version 3.0. Median follow-up was 3 years.Results:The mean change of applicators positions compared to baseline varied substantially between HDR-B fractions, being 1.4 mm before fraction 1 (range, –4 to 2 mm), –13.1 mm before fraction 2 (range, –36 to 0 mm), –4.1 mm before fraction 3 (range, –21 to 9 mm), and –2.6 mm at fraction 4 (range, –16 to 9 mm). The original position of the applicators could be readjusted easily prior to each fraction in every patient. In 18 patients (51%), the applicators were at least once readjusted > 10 mm, however, acute or late grade ≥ 2 genitourinary toxicity was not increased (p = 1.0) in these patients.Conclusion:Caudad position shifts up to 36 mm were observed. Gold markers represent a valuable tool to ensure setup accuracy and precise dose delivery in fractionated HDR-B monotherapy of prostate cancer.Hintergrund und Ziel:Um ein einziges Implantat mit einem Bestrahlungsplan fur die fraktionierte High-Dose-Rate-Brachytherapie (HDR-B) nutzen zu konnen, mussen Positionsverschiebungen der Katheter vor jeder Fraktion erkannt und korrigiert werden. Die Autoren untersuchten den Nutzen von Goldmarkern fur rontgenbildbasierte Konfiguration und Positionskontrolle zwischen den Einzelfraktionen.Patienten und Methodik:Die kraniokaudalen Verschiebungen der Applikatoren wurden vor jeder HDR-B-Fraktion anhand von zwei bis drei Goldmarkern als intraprostatische Referenz und ein bis zwei rontgendicht markierten Referenzapplikatoren mittels Rontgenbild bestimmt. 35 Patienten mit Prostatakarzinom, welche zwischen 10/2003 and 06/2006 eine HDR-B als Monotherapie mit vier Fraktionen von jeweils 9,5 Gy erhielten, wurden untersucht. Die Behandlungstoxizitat wurde mit dem CTCAE-Score, Version 3.0, erfasst. Die mediane Nachbeobachtungszeit lag bei 3 Jahren.Ergebnisse:Die mittlere Positionsabweichung der Applikatoren von der Sollposition variierte erheblich zwischen den HDR-B-Fraktionen und betrug 1,4 mm vor der ersten Fraktion (Spannweite: –4 bis 2 mm), –13,1 mm vor der zweiten Fraktion (Spannweite: –36 bis 0 mm), –4,1 mm vor der dritten Fraktion (Spannweite: –21 bis 9 mm) und –2,6 mm vor der vierten Fraktion (Spannweite: –16 bis 9 mm). Die ursprungliche Position der Applikatoren konnte bei jedem Patienten problemlos vor jeder Fraktion wiederhergestellt werden. Bei 18 Patienten (51%) wurden die Applikatoren wenigstens einmal > 10 mm verschoben; dennoch war die genitourethrale Akut- oder Spattoxizitat Grad ≥ 2 bei diesen Patienten nicht erhoht (p = 1,0).Schlussfolgerung:Positionsverschiebungen von bis zu 36 mm nach kaudal wurden beobachtet. Goldmarker sind bei der fraktionierten HDR-B-Monotherapie des Prostatakarzinoms von Nutzen, um die akkurate Konfiguration und die prazise Verabreichung der Strahlendosis zu gewahrleisten.

Urethral toxicity vs. cancer control—Lessons to be learned from high–dose rate brachytherapy combined with intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

PURPOSE To describe biochemical relapse-free survival (BRFS) and late toxicity after combined high-dose rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT) in intermediate- and high-risk prostate cancer patients. METHODS AND MATERIALS From March 2003 to September 2005, 64 men were treated by 3×7Gy HDR-B using one implant followed by 50Gy IMRT. Median age was 66.1 years; risk of recurrence was intermediate in 30 (47%) or high in 34 (53%) patients. Forty-four (69%) patients received hormonal therapy. Patients were treated with a median of 13 HDR-B applicators (range, 8-17). Biochemical relapse was defined according to Phoenix criteria. Toxicity was scored according to the Common Toxicity Criteria scale version 3.0. RESULTS Median followup was 5.1 years. The 3-year BRFS was 100% and 91% for intermediate- and high-risk patients. Late Grade 2 gastrointestinal (GI) toxicity occurred in 3 (4.7%) patients, late Grade 3 GI toxicity was absent. Late Grade 3 and 4 genitourinary (GU) toxicity was observed in 7 (10.9%) and 2 (3.1%) patients. The 5-year Grade 3 or higher late GU toxicity-free survival was associated with a higher number of HDR-B applicators (p=0.049). CONCLUSIONS The 3-year BRFS was excellent and late GI toxicity was negligible. However, the late Grade 3 and 4 GU toxicity was unacceptably high.